Biomedical subjects

Lihong V Wang

Publications and source records attributed to Lihong V Wang.

At least 19 recordsLinked to original sources

PubMed2007

In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion.

Hypoxia is a critical event in tumor progression and angiogenesis. Hypoxia can be detected noninvasively by a novel spectroscopic photoacoustic tomography technology (SPAT) and this finding is supported by our molecular biology investigation aimed to elucidate the etiopathogenesis of SPAT detected hypoxia and angiogenesis. The present study provides an integrated approach to define oxygen status (hypoxia) of intracranial tumor xenografts using spectroscopic photoacoustic tomography. Brain tumors can be identified based on their distorted vascular architecture and oxygen saturation (SO2) images. Noninvasive in vivo tumor oxygenation imaging using SPAT is based on the spectroscopic absorption differences between oxyhemoglobin (O2Hb) and deoxyhemoblobin (HHb). Sprague-Dawley rats inoculated intracranially with ENU1564, a carcinogen-induced rat mammary adenocarcinoma cell line, were imaged with SPAT three weeks post inoculation. Proteins important for tumor angiogenesis and invasion were detected in hypoxic brain foci identified by SPAT and were elevated compared with control brain. Immunohistochemistry, Western blotting, and semi-quantitative RT-PCR showed that HIF-1 alpha, VEGF-A, and VEGFR2 (Flk-1) protein and mRNA expression levels were significantly higher (P < 0.05) in brain tumor tissues compared to normal brain. Gelatin zymography and RT-PCR demonstrated the upregulation of MMP-9 in tumor foci compared with brain control. Together these results suggest the critical role of hypoxia in driving tumor angiogenesis and invasion through upregulation of target genes important for these functions. Moreover this report validates our hypothesis that a novel noninvasive technology (SPAT) developed in our laboratory is suitable for detection of tumors, hypoxia, and angiogenesis.

Animals↗

PubMed2006

Thermoacoustic tomography with correction for acoustic speed variations.

Thermoacoustic tomography (TAT) is a technique that measures microwave-induced thermoacoustic waves at the boundary of biological tissue and generates images of internal microwave absorption distributions from the measurements. Existing reconstruction algorithms for TAT are based on the assumption that the acoustic properties in the tissue are homogeneous. Biological tissue, however, has heterogeneous acoustic properties, which lead to distortion and blurring of small buried objects in the reconstructed images. In this paper we develop a correction method based on ultrasonic transmission tomography (UTT) to improve the image quality of TAT. Numerical simulations and phantom experiments verify the effectiveness of this correction method.

Acoustics↗

PubMed2006

Correlation transfer equation for ultrasound-modulated multiply scattered light.

In this paper, we develop a temporal correlation transfer equation (CTE) for ultrasound-modulated multiply scattered light. The equation can be used to obtain the time-varying specific intensity of light produced by a nonuniform ultrasound field in optically scattering media that have a heterogeneous distribution of optical parameters. We also develop a Monte Carlo algorithm that can provide the spatial distribution of the optical power spectrum in optically scattering media with focused ultrasound fields, and heterogeneous distributions of optically scattering and absorbing objects. Derivation of the CTE is based on the ladder diagram approximation of the Bethe-Salpeter equation that assumes moderate ultrasound pressures. We expect the CTE to be applicable to a wide spectrum of conditions in the ultrasound-modulated optical tomography of soft biological tissues.

Journal Article↗

PubMed2006

Intense acoustic bursts as a signal-enhancement mechanism in ultrasound-modulated optical tomography.

Biophotonic imaging with ultrasound-modulated optical tomography (UOT) promises ultrasonically resolved imaging in biological tissues. A key challenge in this imaging technique is a low signal-to-noise ratio (SNR). We show significant UOT signal enhancement by using intense time-gated acoustic bursts. A CCD camera captured the speckle pattern from a laser-illuminated tissue phantom. Differences in speckle contrast were observed when ultrasonic bursts were applied, compared with when no ultrasound was applied. When CCD triggering was synchronized with burst initiation, acoustic-radiation-force-induced displacements were detected. To avoid mechanical contrast in UOT images, the CCD camera acquisition was delayed several milliseconds until transient effects of acoustic radiation force attenuated to a satisfactory level. The SNR of our system was sufficiently high to provide an image pixel per acoustic burst without signal averaging. Because of the substantially improved SNR, the use of intense acoustic bursts is a promising signal enhancement strategy for UOT.

Feasibility Studies↗

PubMed2006

In vivo three-dimensional photoacoustic tomography of a whole mouse head.

An in vivo photoacoustic imaging system was designed and implemented to image the entire small animal head. A special scanning gantry was designed to enable in vivo imaging in coronal cross sections with high contrast and good spatial resolution for the first time to our knowledge. By use of a 2.25 MHz ultrasonic transducer with a 6 mm diameter active element, an in-plane radial resolution of approximately 312 microm was achieved. Deeply seated arterial and venous vessels in the head measuring up to 1.7 cm in diameter were simultaneously imaged in vivo with 804 nm wavelength laser excitation of photoacoustic waves.

Animals↗

PubMed2006

Stochastic explanation of speckle contrast detection in ultrasound-modulated optical tomography.

Ultrasound-modulated optical tomography is an imaging technique that detects ultrasonically tagged light in optically turbid media to obtain images with optical contrast and ultrasonic spatial resolution. A CCD-camera-based speckle contrast detection scheme has been introduced previously to detect modulated light emerging from the ultrasonic sample volume. Differences in speckle contrast were experimentally observed when ultrasound was applied compared to when it was not. In this paper we provide an analytic explanation for this phenomenon and connect speckle statistics with ultrasonic field parameters. The theory predicts that speckle contrast changes linearly with applied acoustic intensity. This prediction is experimentally validated for both 1 and ultrasound. Signal dependence on ultrasound frequency is discussed.

Gelatin↗

PubMed2006

Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging.

Although optical absorption is strongly associated with the physiological status of biological tissue, existing high-resolution optical imaging modalities, including confocal microscopy, two-photon microscopy and optical coherence tomography, do not sense optical absorption directly. Furthermore, optical scattering prevents these methods from imaging deeper than approximately 1 mm below the tissue surface. Here we report functional photoacoustic microscopy (fPAM), which provides multiwavelength imaging of optical absorption and permits high spatial resolution beyond this depth limit with a ratio of maximum imaging depth to depth resolution greater than 100. Reflection mode, rather than orthogonal or transmission mode, is adopted because it is applicable to more anatomical sites than the others. fPAM is demonstrated with in vivo imaging of angiogenesis, melanoma, hemoglobin oxygen saturation (sO2) of single vessels in animals and total hemoglobin concentration in humans.

Anatomy, Cross-Sectional↗

PubMed2006

Correlation transfer and diffusion of ultrasound-modulated multiply scattered light.

We develop a temporal correlation transfer equation (CTE) and a temporal correlation diffusion equation (CDE) for ultrasound-modulated multiply scattered light. These equations can be applied to an optically scattering medium with embedded optically scattering and absorbing objects to calculate the power spectrum of light modulated by a nonuniform ultrasound field. We present an analytical solution based on the CDE and Monte Carlo simulation results for light modulated by a cylinder of ultrasound in an optically scattering slab. We further validate with experimental measurements the numerical calculations for an actual ultrasound field. The CTE and CDE are valid for moderate ultrasound pressures and on a length scale comparable with the optical transport mean-free path. These equations should be applicable to a wide spectrum of conditions for ultrasound-modulated optical tomography of soft biological tissues.

Animals↗

PubMed2006

Improved in vivo photoacoustic microscopy based on a virtual-detector concept.

Recently an in vivo high-resolution backward-mode photoacoustic microscope was developed that shows potential for applications in dermatology and related cancer research. However, the limited depth of focus of the large-numerical-aperture (NA) ultrasonic lens employed in this system causes the image quality to deteriorate significantly in the out-of-focus region. To solve this problem, we devised and explored, for the first time to our knowledge, a virtual-detector-based synthetic-aperture focusing technique, combined with coherence weighting, for photoacoustic microscopy with such a large-NA transducer. Images of phantoms show that the proposed technique improves the -6 dB lateral resolution from 49-379 to 46-53 microm and increases the signal-to-noise ratio by up to 29 dB, depending on the distance from the ultrasonic focal point. In vivo experiments show that the technique also provides a clearer representation of the vascular distribution in the rat's scalp.

Algorithms↗

PubMed2006

Rhesus monkey brain imaging through intact skull with thermoacoustic tomography.

Two-dimensional microwave-induced thermoacoustic tomography (TAT) is applied to imaging the Rhesus monkey brain through the intact skull. To reduce the wavefront distortion caused by the skull, only the low-frequency components of the thermoacoustic signals (< 1 MHz) are used to reconstruct the TAT images. The methods of signal processing and image reconstruction are validated by imaging a lamb kidney. The resolution of the system is found to be 4 mm when we image a 1-month-old monkey head containing inserted needles. We also image the coronal and axial sections of a 7-month-old monkey head. Brain features that are 3 cm deep in the head are imaged clearly. Our results demonstrate that TAT has potential for use in portable, cost-effective imagers for pediatric brains.

Acoustics↗

PubMed2006

A born-type approximation method for bioluminescence tomography.

In this paper, we present a Born-type approximation method for bioluminescence tomography (BLT), which is to reconstruct an internal bioluminescent source from the measured bioluminescent signal on the external surface of a small animal. Based on the diffusion approximation for the photon propagation in biological tissue, this BLT method utilizes the Green function to establish a linear relationship between the measured bioluminescent signal and the internal bioluminescent source distribution. The Green function can be modified to describe a heterogeneous medium with an arbitrary boundary using the Born approximation. The BLT reconstruction is formulated in a linear least-squares optimization framework with simple bounds constraint. The performance of this method is evaluated in numerical simulation and phantom experiments.

Algorithms↗

PubMed2005

Synchronous self-elimination of autocorrelation interference in Fourier-domain optical coherence tomography.

We have developed a new algorithm and configuration for self-eliminating the autocorrelation of the object wave in Fourier-domain optical coherence tomography. A self-interferogram of the object wave is acquired synchronously with the standard interferogram of the recombined object and reference waves. The former is then subtracted from the latter after Fourier transformation. The algorithm is validated by numerical simulation and by experimental measurement of a U.S. Air Force target and a feline eye.

Algorithms↗

PubMed2005

Modulation of multiply scattered coherent light by ultrasonic pulses: an analytical model.

We present an analytical solution for the acousto-optical modulation of multiply scattered light in a medium irradiated with a train of ultrasound pulses. Previous theory is extended to cases where the ultrasound-induced optical phase increments between the different scattering events are strongly correlated, and it is shown that the approximate similarity relation still holds. The relation between the ultrasound induced motions of the background fluid and the optical scatterers is generalized, and it is shown that correlation exists between the optical phase increments that are due to the scatterer movement and the optical phase increments that are due to the modulation of the optical index of refraction. Finally, it is shown that compared with the spectrum of ultrasound pulses, the power spectral density of acousto-optically modulated light is strongly attenuated at the higher ultrasound frequencies.

Journal Article↗

PubMed2005

Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation.

We report on a new configuration of fiber-based polarization-sensitive Mueller matrix optical coherence tomography that permits the acquisition of the round-trip Jones matrix of a biological sample using only one light source and a single depth scan. In this new configuration, a polarization modulator is used in the source arm to continuously modulate the incident polarization state for both the reference and the sample arms. The Jones matrix of the sample can be calculated from the two frequency terms in the two detection channels. The first term is modulated by the carrier frequency, which is determined by the longitudinal scanning mechanism, whereas the other term is modulated by the beat frequency between the carrier frequency and the second harmonic of the modulation frequency of the polarization modulator. One important feature of this system is that, for the first time to our knowledge, the Jones matrix of the sample can be calculated with a single detection channel and a single measurement when diattenuation is negligible. The system was successfully tested by imaging both standard polarization elements and biological samples.

Algorithms↗

PubMed2005

In vivo dark-field reflection-mode photoacoustic microscopy.

Reflection-mode photoacoustic microscopy with dark-field laser pulse illumination and high-numerical-aperture ultrasonic detection is designed and implemented in noninvasively imaged blood vessels in the skin in vivo. Dark-field optical illumination minimizes the interference caused by strong photoacoustic signals from superficial structures. A high-numerical-aperture acoustic lens provides high lateral resolution, 45-120 microm in this system. A broadband ultrasonic detection system provides high axial resolution, estimated to be approximately 15 microm. The optical illumination and ultrasonic detection are in a coaxial confocal configuration for optimal image quality. The system is capable of imaging optical-absorption contrast as deep as 3 mm in biological tissue.

Animals↗

PubMed2005

Deeply penetrating photoacoustic tomography in biological tissues enhanced with an optical contrast agent.

Photoacoustic tomography (PAT) in a circular scanning configuration was developed to image deeply embedded optical heterogeneity in biological tissues. While the optical penetration was maximized with near-infrared laser pulses of 800-nm wavelength, the optical contrast was enhanced by Indocyanine Green (ICG) dye whose absorption peak matched the laser wavelength. This optimized PAT was able to image objects embedded at depths of as much as 5.2 cm, 6.2 times the 1/e optical penetration depth, in chicken breast muscle at a resolution of <780 microm and a sensitivity of <7 pmol of ICG in blood. The resolution was found to deteriorate slowly with increasing imaging depth. The effects of detection bandwidth on the quality of images acquired simultaneously by four different ultrasonic transducers are described.

Animals↗

PubMed2005

Imaging of tumor angiogenesis in rat brains in vivo by photoacoustic tomography.

Green laser pulses at a wavelength of 532 nm from a Q-switched Nd:YAG laser were employed as irradiation sources for photoacoustic tomography (PAT). The vascular structure of the brain was imaged clearly, with optimal contrast, because blood has strong absorption near this wavelength. The photoacoustic images of rat brain tumors in this study clearly reveal the angiogenesis that is associated with tumors. Brain tumors can be identified based on the distorted vascular architecture of brain tumorigenesis and related vascular changes, such as hemorrhage. This research demonstrates that PAT can potentially provide a powerful tool for small-animal biological research.

Acoustics↗

PubMed2005

Universal back-projection algorithm for photoacoustic computed tomography.

We report results of a reconstruction algorithm for three-dimensional photoacoustic computed tomography. A universal back-projection formula is presented for three types of imaging geometries: planar, spherical, and cylindrical surfaces. A solid-angle weighting factor is introduced in the back-projection formula to compensate for the variations of detection views. A method for implementing this algorithm is described. Numerical simulation is used to demonstrate the performance of the algorithm.

Acoustics↗